Neutrophil activation with subsequent damage to host tissues during septicemia has been implicated in the cascade of events that lead to multiple organ failure (MOF). MOF is associated with over half of all deaths from septic shock. The mediators and mechanisms responsible for neutrophil "overactivation" and organ injury are not completely understood. In this study, we have measured concentrations of Neutrophil Activating Protein-I (NAP-I), a recently described macrophage derived cytokine (now designated Interleukin 8), in the serum of patients with septic shock and in the bronchoalveolar lavage fluid of patients with the adult Respiratory Distress Syndrome. A recent initiative in this project involved the identification and characterization of circulating IL-8 binding protein(s) in septic shock. This line of investigation arose from the finding of interference in the ELISA assay in some septic patients (J Immunol, 1993). Further, in vitro priming by IL-8 has been examined in detail and intercellular mechanisms that control IL-8 production are actively under investigation. This investigation will provide insight into the mechanisms of organ damage in septic shock. This understanding may lead to the development of new therapies for septic shock aimed at inhibiting or regulating potentially harmful endogenous mediators of the inflammatory response.